Journal of Cardiac Failure
Volume 13, Issue 4 , Pages 294-303 , May 2007

Effect of Exercise Training on Autonomic Derangement and Neurohumoral Activation in Chronic Heart Failure

  • Maaike G.J. Gademan, MSc

      Affiliations

    • Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
    • ,
  • Cees A. Swenne, PhD

      Affiliations

    • Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
    • Corresponding Author InformationReprint requests: Cees A. Swenne, PhD, Department of Cardiology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
    • ,
  • Harriette F. Verwey, MD

      Affiliations

    • Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
    • ,
  • Arnoud van der Laarse, PhD

      Affiliations

    • Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
    • ,
  • Arie C. Maan, PhD

      Affiliations

    • Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
    • ,
  • Hedde van de Vooren, MSc

      Affiliations

    • Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
    • ,
  • Johannes van Pelt, PhD

      Affiliations

    • Department of Clinical Chemistry, Leiden University Medical Center, Leiden, The Netherlands
    • ,
  • Henk J. van Exel, MD

      Affiliations

    • Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
    • Deparment of Cardiopulmonary Rehabilitation, Rijnland Rehabilitation Center, Leiden, The Netherlands
    • ,
  • Caroline M.H.B. Lucas, MD

      Affiliations

    • Heart Failure Outpatient Clinic, Rijnland Hospital, Leiderdorp, The Netherlands
    • ,
  • Ger V.J. Cleuren, RN

      Affiliations

    • Heart Failure Outpatient Clinic, Rijnland Hospital, Leiderdorp, The Netherlands
    • ,
  • Soeresh Somer, MD

      Affiliations

    • Regional Heart Rehabilitation Center, Bronovo Hospital, Den Haag, The Netherlands
    • ,
  • Martin J. Schalij, MD

      Affiliations

    • Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
    • ,
  • Ernst E. van der Wall, MD

      Affiliations

    • Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands

Received 9 May 2006 ,Revised 15 December 2006 ,Accepted 27 December 2006.

References 

  1. Frenneaux MP. Autonomic changes in patients with heart failure and in post-myocardial infarction patients. Heart. 2004;90:1248–1255
  2. Grassi G, Seravalle G, Cattaneo BM, Lanfranchi A, Vailati S, Giannattasio C, et al. Sympathetic activation and loss of reflex sympathetic control in mild congestive heart failure. Circulation. 1995;92:3206–3211
  3. Gao L, Schultz HD, Patel KP, Zucker IH, Wang W. Augmented input from cardiac sympathetic afferents inhibits baroreflex in rats with heart failure. Hypertension. 2005;45:1173–1181
  4. Zucker IH, Wang W, Pliquett RU, Liu JL, Patel KP. The regulation of sympathetic outflow in heart failure. The roles of angiotensin II, nitric oxide, and exercise training. Ann N Y Acad Sci. 2001;940:431–443
  5. Rundqvist B, Elam M, Bergmann-Sverrisdottir Y, Eisenhofer G, Friberg P. Increased cardiac adrenergic drive precedes generalized sympathetic activation in human heart failure. Circulation. 1997;95:169–175
  6. Hein S, Arnon E, Kostin S, Schonburg M, Elsasser A, Polyakova V, et al. Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: structural deterioration and compensatory mechanisms. Circulation. 2003;107:984–991
  7. Cinquegrana G, D'Aniello L, Landi M, Spinelli L, Grande G, De Prisco F, et al. Effects of different degrees of sympathetic antagonism on cytokine network in patients with ischemic dilated cardiomyopathy. J Card Fail. 2005;11:213–219
  8. Kan H, Xie Z, Finkel MS. Norepinephrine-stimulated MAP kinase activity enhances cytokine-induced NO production by rat cardiac myocytes. Am J Physiol. 1999;276:H47–H52
  9. Marks AR. Cardiac intracellular calcium release channels: role in heart failure. Circ Res. 2000;87:8–11
  10. Gosker HR, Wouters EF, van der Vusse GJ, Schols AM. Skeletal muscle dysfunction in chronic obstructive pulmonary disease and chronic heart failure: underlying mechanisms and therapy perspectives. Am J Clin Nutr. 2000;71:1033–1047
  11. Itoh K, Osada N, Inoue K, Samejima H, Seki A, Omiya K, et al. Relationship between exercise intolerance and levels of neurohormonal factors and proinflammatory cytokines in patients with stable chronic heart failure. Int Heart J. 2005;46:1049–1059
  12. Piepoli M, Clark AL, Volterrani M, Adamopoulos S, Sleight P, Coats AJ. Contribution of muscle afferents to the hemodynamic, autonomic, and ventilatory responses to exercise in patients with chronic heart failure: effects of physical training. Circulation. 1996;93:940–952
  13. DeBakey ME. Development of mechanical heart devices. Ann Thorac Surg. 2005;79:S2228–S2231
  14. Swedberg K, Cleland J, Dargie H, Drexler H, Follath F, Komajda M, et al. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): the Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J. 2005;26:1115–1140
  15. Patten RD, Kronenberg MW, Benedict CR, Udelson JE, Kinan D, Stewart D, et al. Acute and long-term effects of the angiotensin-converting enzyme inhibitor, enalapril, on adrenergic activity and sensitivity during exercise in patients with left ventricular systolic dysfunction. Am Heart J. 1997;134:37–43
  16. Tendera M, Ochala A. Overview of the results of recent beta blocker trials. Curr Opin Cardiol. 2001;16:180–185
  17. Roger VL, Weston SA, Redfield MM, Hellermann-Homan JP, Killian J, Yawn BP, et al. Trends in heart failure incidence and survival in a community-based population. JAMA. 2004;292:344–350
  18. Bleumink GS, Knetsch AM, Sturkenboom MC, Straus SM, Hofman A, Deckers JW, et al. Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure The Rotterdam Study. Eur Heart J. 2004;25:1614–1619
  19. Benedict CR, Shelton B, Johnstone DE, Francis G, Greenberg B, Konstam M, et al. Prognostic significance of plasma norepinephrine in patients with asymptomatic left ventricular dysfunction. SOLVD Investigators. Circulation. 1996;94:690–697
  20. Anand IS, Fisher LD, Chiang YT, Latini R, Masson S, Maggioni AP, et al. Changes in brain natriuretic peptide and norepinephrine over time and mortality and morbidity in the Valsartan Heart Failure Trial (Val-HeFT). Circulation. 2003;107:1278–1283
  21. Kubo T, Parker JD, Azevedo ER, Atchison DJ, Newton GE, Picton P, et al. Vagal heart rate responses to chronic beta-blockade in human heart failure relate to cardiac norepinephrine spillover. Eur J Heart Fail. 2005;7:878–881
  22. Mortara A, La Rovere MT, Pinna GD, Maestri R, Capomolla S, Cobelli F. Nonselective beta-adrenergic blocking agent, carvedilol, improves arterial baroflex gain and heart rate variability in patients with stable chronic heart failure. J Am Coll Cardiol. 2000;36:1612–1618
  23. Sanderson JE, Yeung LY, Chan S, Tomlinson B, Kay R, Woo KS, et al. Effect of beta-blockade on baroreceptor and autonomic function in heart failure. Clin Sci (Lond). 1999;96:137–146
  24. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, et al. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult—summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation. 2005;112:1825–1852
  25. McKelvie RS, Teo KK, Roberts R, McCartney N, Humen D, Montague T, et al. Effects of exercise training in patients with heart failure: the Exercise Rehabilitation Trial (EXERT). Am Heart J. 2002;144:23–30
  26. Hambrecht R, Gielen S, Linke A, Fiehn E, Yu J, Walther C, et al. Effects of exercise training on left ventricular function and peripheral resistance in patients with chronic heart failure: A randomized trial. JAMA. 2000;283:3095–3101
  27. Austin J, Williams R, Ross L, Moseley L, Hutchison S. Randomised controlled trial of cardiac rehabilitation in elderly patients with heart failure. Eur J Heart Fail. 2005;7:411–417
  28. Belardinelli R, Georgiou D, Cianci G, Purcaro A. Randomized, controlled trial of long-term moderate exercise training in chronic heart failure: effects on functional capacity, quality of life, and clinical outcome. Circulation. 1999;99:1173–1182
  29. Oka RK, De Marco T, Haskell WL, Botvinick E, Dae MW, Bolen K, et al. Impact of a home-based walking and resistance training program on quality of life in patients with heart failure. Am J Cardiol. 2000;85:365–369
  30. Parnell MM, Holst DP, Kaye DM. Exercise training increases arterial compliance in patients with congestive heart failure. Clin Sci (Lond). 2002;102:1–7
  31. Tyni-Lenne R, Dencker K, Gordon A, Jansson E, Sylven C. Comprehensive local muscle training increases aerobic working capacity and quality of life and decreases neurohormonal activation in patients with chronic heart failure. Eur J Heart Fail. 2001;3:47–52
  32. Delagardelle C, Feiereisen P, Autier P, Shita R, Krecke R, Beissel J. Strength/endurance training versus endurance training in congestive heart failure. Med Sci Sports Exerc. 2002;34:1868–1872
  33. Piepoli MF, Davos C, Francis DP, Coats AJ. Exercise training metaanalysis of trials in patients with chronic heart failure (ExTraMATCH). BMJ. 2004;328:189
  34. Smart N, Marwick TH. Exercise training for patients with heart failure: a systematic review of factors that improve mortality and morbidity. Am J Med. 2004;116:693–706
  35. Rees K, Taylor RS, Singh S, Coats AJ, Ebrahim S. Exercise based rehabilitation for heart failure. Cochrane Database Syst Rev. 2004;3:CD003331
  36. De Sutter JHAJ, Ascoop AK, Van de Veire N, De Winter O, Salhi B, De Backer G. Exercise training results in a significant reduction of mortality and morbidity in heart failure patients on optimal medical treatment. Eur Heart J. 2005;(Suppl):26;abstract 370
  37. Giannuzzi P, Temporelli PL, Corra U, Tavazzi L. Antiremodeling effect of long-term exercise training in patients with stable chronic heart failure: results of the Exercise in Left Ventricular Dysfunction and Chronic Heart Failure (ELVD-CHF) Trial. Circulation. 2003;108:554–559
  38. Pina IL, Apstein CS, Balady GJ, Belardinelli R, Chaitman BR, Duscha BD, et al. Exercise and heart failure: a statement from the American Heart Association Committee on exercise, rehabilitation, and prevention. Circulation. 2003;107:1210–1225
  39. Hambrecht R, Fiehn E, Yu J, Niebauer J, Weigl C, Hilbrich L, et al. Effects of endurance training on mitochondrial ultrastructure and fiber type distribution in skeletal muscle of patients with stable chronic heart failure. J Am Coll Cardiol. 1997;29:1067–1073
  40. Gordon A, Tyni-Lenne R, Persson H, Kaijser L, Hultman E, Sylven C. Markedly improved skeletal muscle function with local muscle training in patients with chronic heart failure. Clin Cardiol. 1996;19:568–574
  41. Piepoli MF, Scott AC, Capucci A, Coats AJ. Skeletal muscle training in chronic heart failure. Acta Physiol Scand. 2001;171:295–303
  42. Keteyian SJ, Brawner CA, Schairer JR, Levine TB, Levine AB, Rogers FJ, et al. Effects of exercise training on chronotropic incompetence in patients with heart failure. Am Heart J. 1999;138:233–240
  43. Dubach P, Myers J, Dziekan G, Goebbels U, Reinhart W, Muller P, et al. Effect of high intensity exercise training on central hemodynamic responses to exercise in men with reduced left ventricular function. J Am Coll Cardiol. 1997;29:1591–1598
  44. Braith RW, Edwards DG. Neurohormonal abnormalities in heart failure: impact of exercise training. Congest Heart Fail. 2003;9:70–76
  45. Zheng H, Li YF, Zucker IH, Patel KP. Exercise training improves renal excretory responses to acute volume expansion in rats with heart failure. Am J Physiol Renal Physiol. 2006;291:F1148–F1156
  46. Larsen AI, Dickstein K. Exercise training in congestive heart failure. A review of the current status. Minerva Cardioangiol. 2005;53:275–286
  47. Passino C, Severino S, Poletti R, Piepoli MF, Mammini C, Clerico A, et al. Aerobic training decreases B-type natriuretic peptide expression and adrenergic activation in patients with heart failure. J Am Coll Cardiol. 2006;47:1835–1839
  48. Experience from controlled trials of physical training in chronic heart failure. Protocol and patient factors in effectiveness in the improvement in exercise tolerance. European Heart Failure Training Group. Eur Heart J. 1998;19:466–475
  49. Yeh GY, Wood MJ, Lorell BH, Stevenson LW, Eisenberg DM, Wayne PM, et al. Effects of tai chi mind-body movement therapy on functional status and exercise capacity in patients with chronic heart failure: a randomized controlled trial. Am J Med. 2004;117:541–548
  50. Ainsworth BE, Haskell WL, Whitt MC, Irwin ML, Swartz AM, Strath SJ, et al. Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc. 2000;32(Suppl):S498–S504
  51. Opie LH. Heart phyiology; from cell to circulation, 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2004;
  52. Mortara A, La Rovere MT, Pinna GD, Prpa A, Maestri R, Febo O, et al. Arterial baroreflex modulation of heart rate in chronic heart failure: clinical and hemodynamic correlates and prognostic implications. Circulation. 1997;96:3450–3458
  53. Buch AN, Coote JH, Townend JN. Mortality, cardiac vagal control and physical training—what's the link?. Exp Physiol. 2002;87:423–435
  54. La Rovere MT, Bersano C, Gnemmi M, Specchia G, Schwartz PJ. Exercise-induced increase in baroreflex sensitivity predicts improved prognosis after myocardial infarction. Circulation. 2002;106:945–949
  55. Mimura J, Yuasa F, Yuyama R, Kawamura A, Iwasaki M, Sugiura T, et al. The effect of residential exercise training on baroreflex control of heart rate and sympathetic nerve activity in patients with acute myocardial infarction. Chest. 2005;127:1108–1115
  56. Pietila M, Malminiemi K, Vesalainen R, Jartti T, Teras M, Nagren K, et al. Exercise training in chronic heart failure: beneficial effects on cardiac (11)C-hydroxyephedrine PET, autonomic nervous control, and ventricular repolarization. J Nucl Med. 2002;43:773–779
  57. Van de Vooren H, Gademan MGJ, Swenne CA, Ten Voorde BJ, Schalij MJ, Van der Wall EE. Baroreflex sensitivity, blood pressure buffering and resonance: what are the links? Computer simulation of healthy subjects and heart failure patients. J Appl Physiol 2007;102:1348–56.
  58. Frederiks J, Swenne CA, TenVoorde BJ, Honzikova N, Levert JV, Maan AC, et al. The importance of high-frequency paced breathing in spectral baroreflex sensitivity assessment. J Hypertens. 2000;18:1635–1644
  59. Guzzetti S, Magatelli R, Borroni E, Mezzetti S. Heart rate variability in chronic heart failure. Auton Neurosci. 2001;90:102–105
  60. Nolan J, Batin PD, Andrews R, Lindsay SJ, Brooksby P, Mullen M, et al. Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart). Circulation. 1998;98:1510–1516
  61. Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J. 1996;17:354–381
  62. Adamopoulos S, Ponikowski P, Cerquetani E, Piepoli M, Rosano G, Sleight P, et al. Circadian pattern of heart rate variability in chronic heart failure patients. Effects of physical training. Eur Heart J. 1995;16:1380–1386
  63. Coats AJ, Adamopoulos S, Radaelli A, McCance A, Meyer TE, Bernardi L, et al. Controlled trial of physical training in chronic heart failure. Exercise performance, hemodynamics, ventilation, and autonomic function. Circulation. 1992;85:2119–2131
  64. Selig SE, Carey MF, Menzies DG, Patterson J, Geerling RH, Williams AD, et al. Moderate-intensity resistance exercise training in patients with chronic heart failure improves strength, endurance, heart rate variability, and forearm blood flow. J Card Fail. 2004;10:21–30
  65. Klabunde RE. Cardiovascular physiology concepts. Philadelphia: Lippincott Williams & Wilkins; 2005;
  66. Rea RF, Eckberg DL, Fritsch JM, Goldstein DS. Relation of plasma norepinephrine and sympathetic traffic during hypotension in humans. Am J Physiol. 1990;258:R982–R986
  67. Belardinelli R, Georgiou D, Scocco V, Barstow TJ, Purcaro A. Low intensity exercise training in patients with chronic heart failure. J Am Coll Cardiol. 1995;26:975–982
  68. Hambrecht R, Niebauer J, Fiehn E, Kalberer B, Offner B, Hauer K, et al. Physical training in patients with stable chronic heart failure: effects on cardiorespiratory fitness and ultrastructural abnormalities of leg muscles. J Am Coll Cardiol. 1995;25:1239–1249
  69. Keteyian SJ, Levine AB, Brawner CA, Kataoka T, Rogers FJ, Schairer JR, et al. Exercise training in patients with heart failure. A randomized, controlled trial. Ann Intern Med. 1996;124:1051–1057
  70. Kiilavuori K, Naveri H, Leinonen H, Harkonen M. The effect of physical training on hormonal status and exertional hormonal response in patients with chronic congestive heart failure. Eur Heart J. 1999;20:456–464
  71. Kobayashi N, Tsuruya Y, Iwasawa T, Ikeda N, Hashimoto S, Yasu T, et al. Exercise training in patients with chronic heart failure improves endothelial function predominantly in the trained extremities. Circ J. 2003;67:505–510
  72. Tyni-Lenne R, Gordon A, Jensen-Urstad M, Dencker K, Jansson E, Sylven C. Aerobic training involving a minor muscle mass shows greater efficiency than training involving a major muscle mass in chronic heart failure patients. J Card Fail. 1999;5:300–307
  73. Gordon A, Tyni-Lenne R, Jansson E, Kaijser L, Theodorsson-Norheim E, Sylven C. Improved ventilation and decreased sympathetic stress in chronic heart failure patients following local endurance training with leg muscles. J Card Fail. 1997;3:3–12
  74. Mello Franco FG, Santos AC, Rondon MU, Trombetta IC, Strunz C, Braga AM, et al. Effects of home-based exercise training on neurovascular control in patients with heart failure. Eur J Heart Fail. 2006;8:851–855
  75. Roveda F, Middlekauff HR, Rondon MU, Reis SF, Souza M, Nastari L, et al. The effects of exercise training on sympathetic neural activation in advanced heart failure: a randomized controlled trial. J Am Coll Cardiol. 2003;42:854–860
  76. Weir MR, Dzau VJ. The renin-angiotensin-aldosterone system: a specific target for hypertension management. Am J Hypertens. 1999;12:205S–213S
  77. Kurdi M, De Mello WC, Booz GW. Working outside the system: an update on the unconventional behavior of the renin-angiotensin system components. Int J Biochem Cell Biol. 2005;37:1357–1367
  78. Opie LH. The neuroendocrinology of congestive heart failure. Cardiovasc J S Afr. 2002;13:171–178
  79. Chun TY, Bloem LJ, Pratt JH. Aldosterone inhibits inducible nitric oxide synthase in neonatal rat cardiomyocytes. Endocrinology. 2003;144:1712–1717
  80. Schmidt BM, Horisberger K, Feuring M, Schultz A, Wehling M. Aldosterone blunts human baroreflex sensitivity by a nongenomic mechanism. Exp Clin Endocrinol Diabetes. 2005;113:252–256
  81. Braith RW, Welsch MA, Feigenbaum MS, Kluess HA, Pepine CJ. Neuroendocrine activation in heart failure is modified by endurance exercise training. J Am Coll Cardiol. 1999;34:1170–1175
  82. Lee CR, Watkins ML, Patterson JH, Gattis W, O'connor CM, Gheorghiade M, et al. Vasopressin: a new target for the treatment of heart failure. Am Heart J. 2003;146:9–18
  83. Goldsmith SR, Francis GS, Cowley AW, Levine TB, Cohn JN. Increased plasma arginine vasopressin levels in patients with congestive heart failure. J Am Coll Cardiol. 1983;1:1385–1390
  84. Derick S, Cheng LL, Voirol MJ, Stoev S, Giacomini M, Wo NC, et al. [1-deamino-4-cyclohexylalanine] arginine vasopressin: a potent and specific agonist for vasopressin V1b receptors. Endocrinology. 2002;143:4655–4664
  85. Chatterjee K. Neurohormonal activation in congestive heart failure and the role of vasopressin. Am J Cardiol. 2005;95:8B–13B
  86. Nishida Y, Bishop VS. Vasopressin-induced suppression of renal sympathetic outflow depends on the number of baroafferent inputs in rabbits. Am J Physiol. 1992;263:R1187–R1194
  87. Charmandari E, Tsigos C, Chrousos G. Endocrinology of the stress response. Annu Rev Physiol. 2005;67:259–284
  88. Levin ER. Endothelins. N Engl J Med. 1995;333:356–363
  89. Wei CM, Lerman A, Rodeheffer RJ, McGregor CG, Brandt RR, Wright S, et al. Endothelin in human congestive heart failure. Circulation. 1994;89:1580–1586
  90. Rademaker MT, Richards AM. Cardiac natriuretic peptides for cardiac health. Clin Sci (Lond). 2005;108:23–36
  91. Ruskoaho H. Cardiac hormones as diagnostic tools in heart failure. Endocr Rev. 2003;24:341–356
  92. Doust JA, Pietrzak E, Dobson A, Glasziou P. How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review. BMJ. 2005;330:625
  93. Conraads VM, Beckers P, Vaes J, Martin M, Van H, V, De Maeyer C, et al. Combined endurance/resistance training reduces NT-proBNP levels in patients with chronic heart failure. Eur Heart J 2004;25:1797–805.
  94. Jonsdottir S, Andersen KK, Sigurethsson AF, Sigurethsson SB. The effect of physical training in chronic heart failure. Eur J Heart Fail. 2006;8:97–101
  95. Maria SF, Gristina T, Brusca I, Milia S, Raimondi R, Sajeva M, et al. Effect of physical training on exercise capacity, gas exchange and N terminal pro-brain natriuretic peptide levels in patients with chronic heart failure. Eur J Cardiovasc Prev Rehabil. 2006;13:812–817
  96. Larsen AI, Gjesdal K, Hall C, Aukrust P, Aarsland T, Dickstein K. Effect of exercise training in patients with heart failure: a pilot study on autonomic balance assessed by heart rate variability. Eur J Cardiovasc Prev Rehabil. 2004;11:162–167

 Financial support by The Netherlands Heart Foundation (grant 2003B094) is gratefully acknowledged.

PII: S1071-9164(06)01298-X

doi: 10.1016/j.cardfail.2006.12.006

Journal of Cardiac Failure
Volume 13, Issue 4 , Pages 294-303 , May 2007

Article Tools

* Image Usage & Resolution